This invention relates to a method of using heat shock protein 70 preparations obtained from tumor cells or cells infected with a virus or other agent in order to elicit an immune response against the tumor, virus or other agent.
The observation that inbred mice and rats can be immunized against their own tumors or tumors of the same genetic background have led to a hypothesis that tumor-specific antigens exist. In essence, these studies showed that mice vaccinated with inactivated cancer cells are immune to subsequent challenges of live cancer cells. The phenomenon was shown to be individually tumor-specific, in that mice were immune specifically to the tumors used to immunize them and not to other tumors. The demonstration of immunogenicity of cancer cells led to a search for the cancer-derived molecules which elicit resistance to tumor challenges. The general approach in these experiments was to fractionate cancer-derived proteins and test them individually for their ability to immunize mice against the cancers from which the fractions were prepared.
One of the major difficulties in cancer immunotherapy has been the possibility that similar to the situation among animal cancers, each human cancer is different from all other cancers, i.e., human cancers, like cancers of experimental animals, are antigenically distinct. Clearly, there is some recent evidence for existence of common human tumor antigens (Kawakami et al., 1991, Darrow et al., 1989), and this augurs well for prospects of cancer immunotherapy. Nonetheless, in light of the overwhelming evidence from experimental and human systems, it is reasonable to assume that at the very least, human tumors would show tremendous antigenic diversity and heterogeneity.
The prospect of identification of the immunogenic antigens of individual tumors from cancer patients (or even of xe2x80x98onlyxe2x80x99 several different types of immunogenic antigens in case the antigens are shared), is daunting to the extent of being impractical. Numerous studies on vaccination against infectious diseases have shown that it is necessary to first identify and characterize the immunogenic antigens.
For the reasons described above, such a strategy is impractical for vaccination or other forms of immunotherapy against human cancers. Thus, there is a need to develop alternate methods for obtaining antigenic preparations which do not require such daunting identification of specific antigens from tumors of individual patients and avoids the difficulties and hazards associated with attenuation and inactivation of viruses.
This invention relates to an immunogenic composition comprising complexes of heat shock protein 70 and antigenic peptides derived from tumor cells or cells infected with a virus, bacteria or other agent. This invention also relates to a method of eliciting an immune response in a mammal comprising the steps of isolating heat shock protein 70-peptide complex from tumor cells or cells infected with a virus, bacteria or other agent and administering the heat shock protein 70-peptide complex to the mammal in an amount effective to elicit an immune response. The claimed invention provides a novel method of eliciting antigen-specific cellular immunity against tumors, endogenous antigens, bacterial and viral antigens.
This invention further relates to a method of preparing a heat shock protein 70-peptide complex capable of eliciting an immune response in a mammal comprising the steps of obtaining tumor cells from the mammal or cells which are infected with a virus, bacteria or other infectious agent, preparing an aqueous cell extract, purifying the extract through column chromatography and harvesting a heat shock protein 70-peptide complex in the absence of adenosine triphosphate (ATP).
This invention additionally relates to a method of preparing an antigenic peptide composition comprising obtaining cells from a mammal wherein the cells are tumor cells or cells infected with a virus, bacteria or other infectious agent, harvesting a heat shock protein 70-peptide complex from the cells wherein the heat shock protein 70-peptide complex is prepared in the absence of ATP and separating peptides from the heat shock protein 70-peptide complex, wherein the separated peptides are capable of eliciting an immune response in the mammal.
This invention also relates to an immunogenic composition comprising complexes of heat shock protein 70 and antigenic peptides derived from tumor cell lines or cell lines infected with a virus or bacteria. The invention further relates to a method of preparing a heat shock protein 70-peptide complex capable of eliciting an immune response in a mammal comprising preparing an aqueous cell extract from tumor cell lines or cell lines infected with a bacteria or virus, purifying the extract through column chromatography and harvesting a heat shock protein 70-peptide complex in the absence of ATP.